Molecular Imaging Using Ultrasound and Targeted Microbubbles

本项目研究超声和微泡在分子成像中的应用。分子成像，有时被称为靶向成像，是大多数人所熟悉的正常解剖成像的一种变化。在分子成像中，目的是在细胞或分子水平上揭示被研究组织的生理功能。这是通过使用一种专门针对特定细胞和分子的标记来完成的。这项技术在诊断癌症、神经系统和心血管疾病等疾病方面具有广泛的潜力。它还可以通过对新药进行详细的临床前和临床试验，在改善许多疾病的治疗方面发挥作用。传统超声成像是最常用的临床成像方式之一。该技术的主要优点是技术的实用性、对患者的风险极低、实时性和相对较低的成本。超声成像的最新进展是微泡造影剂的发展。这些微泡被注射到病人的血液中。它们的作用是增加分散的超声信号，使血液在超声图像上显示得更清晰。超声微泡成像在临床实践中得到越来越多的认可。微泡由一个被薄壳包裹的气体核心组成，通常由脂质单层或交联白蛋白构成，通常与我们血液中循环的红细胞大小相同。微泡的声学特性与悬浮在病人血液中的微泡截然不同。即使是一个单一的气泡也能产生明显的、特定的超声波回声。超声造影增强成像利用这些差异和新兴的临床应用包括诊断心肌灌注和恶性肿瘤血管生成。通过将活性生物标记物整合到微泡壳中，它们可以针对体内的特定分子。这些分子只在特定的生理或病理条件下存在于体内的某些部位。例如，微泡可以被设计成附着在只存在于血管壁炎症区域的分子上。然后可以用超声波检测到被粘住的微气泡。这种新方法引起了全世界基础科学家和临床研究人员对研究界的兴趣。通过这项研究，我们的目标是解决两个主要挑战：首先，使微气泡有效地粘在目标上，并且一旦粘在目标上，它们就能保持足够长的稳定时间。其次，提高超声成像的特异性，使粘滞的微泡与仍在自由流动的微泡在超声图像中得以区分。在这个项目中，我们的目标是改进微泡和用于检测它们的超声技术。我们将开发制造和评估新型靶向微泡的方法。这些微泡的性能将在它们与目标结合的效率和强度以及它们在超声波下的可见性方面得到优化。同时，我们将开发一个声学和光学相结合的实验系统，深入研究这些目标微泡的物理性质。这将能够更详细地优化微泡制造过程，并帮助我们识别和理解它们在附着到目标上后的行为差异。这种理解将使我们能够开发新的和更有效的分子图像方法。在此基础上，我们将开发新的靶向微泡选择性成像技术，并解决组织运动的混淆问题。

This project investigates the use of ultrasound and microbubbles for molecular imaging. Molecular imaging, sometimes referred to as targeted imaging, is a variation of the normal anatomical imaging familiar to most people. In molecular imaging, the aim is to reveal the physiological function of the tissues under investigation at a cellular or molecular level. This is done by using a marker designed to target specific cells and molecules. The technique has widespread potential for the diagnosis of diseases such as cancer, and neurological and cardiovascular diseases. It also has a role to play in improving treatment of many disorders by enabling detailed pre-clinical and clinical tests of new medication. Traditional ultrasound imaging is one of the most frequently used clinical imaging modalities. The primary advantages of the technique are the practicality of the technique, the very low risk to patients, the real-time nature, and the relatively low cost. A recent advance in ultrasound imaging is the development of microbubble contrast agents. The microbubbles are injected into the blood stream of the patient. They act to increase the scattered ultrasound signals, making the blood appear more clearly on the ultrasound image. Ultrasound imaging with microbubbles is gaining acceptance in clinical practice. The microbubbles consist of a gas core that is encapsulated by a thin shell, typically constructed of a lipid monolayer or cross-linked albumin and are typically the same size as the red blood cells that circulate within our blood. The microbubbles have acoustic properties very different from the patient's blood in which they are suspended. Even a single bubble can create significant and specific ultrasound echoes. Ultrasound contrast enhanced imaging exploits these differences and emerging clinical applications include diagnosis of myocardial perfusion and angiogenesis in malignant tumours. By incorporating active biological markers into the microbubble shells, they can be targeted to specific molecules within the body. These molecules only exist at certain sites within the body and under specific physiological or pathological conditions. For example, the microbubbles can be designed to stick to molecules that only exist in areas of inflammation on vessel walls. The stuck microbubbles can then be detected using ultrasound. This new approach is provoking worldwide interest in the research community from both basic scientists and clinical researchers.There are two major challenges that we aim to address through this research: Firstly to make the microbubbles stick effectively and only to the targets of interest, and for them to remain stable for a sufficient length of time once stuck. Secondly to improve the specificity of the ultrasound imaging so that the stuck microbubbles can be differentiated from those still flowing freely in the ultrasound images that are used to detect them.In this project, we aim to improve both the microbubbles and the ultrasound technique used to detect them. We will develop methodology for fabrication and evaluation of novel targeted microbubbles. The performance of these microbubbles will be optimised in terms of the efficiency and strength of their binding to the target and their visibility under ultrasound. At the same time, we will develop a combined acoustic and optical experimental system and thoroughly investigate the physical properties of these targeted microbubbles. This will enable more detailed optimisation of the microbubble fabrication process and help us identify and understand how their behaviour differs once they are attached to the target. This understanding will allow us to develop new and more effective molecular image approaches. Based on these we will develop novel techniques for selective imaging of targeted microbubbles and address the confounding issue of tissue motion.